Skip to main content

Advertisement

SpringerLink
Log in

RETRACTED ARTICLE: The role of fibroblast activation protein in progression and development of osteosarcoma cells

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

This article was retracted on 17 October 2023

This article has been updated

Abstract

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Change history

References

  1. Xuan C, Jin M, Gao Y, et al. miR-218 suppresses the proliferation of osteosarcoma through downregulation of E2F2. Oncol Lett. 2019;17:571–7.

    CAS  PubMed  Google Scholar 

  2. Fontanella R, Pelagalli A, Nardelli A, et al. A novel antagonist of CXCR2 prevents bone marrow-derived mesenchymal stem cell-mediated osteosarcoma and hepatocellular carcinoma cell migration and invasion. Cancer Lett. 2016;370:100–7.

    Article  CAS  PubMed  Google Scholar 

  3. Wong KC, Lee V, Shing MM, Kumta S. Surgical resection of relapse may improve postrelapse survival of patients with localized osteosarcoma. Clin Orthop Relat Res. 2013;471:814–9.

    Article  PubMed  Google Scholar 

  4. Heishima K, Meuten T, Yoshida K, Mori T, Thamm DH. Prognostic significance of circulating microRNA-214 and -126 in dogs with appendicular osteosarcoma receiving amputation and chemotherapy. BMC Vet Res. 2019;15:39.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wu CL, Tsai HC, Chen ZW, et al. Ras activation mediates WISP-1-induced increases in cell motility and matrix metalloproteinase expression in human osteosarcoma. Cell Signal. 2013;25:2812–22.

    Article  CAS  PubMed  Google Scholar 

  6. Ying S, Jianjun H, Xue Y, et al. MicroRNA-133b inhibits cell proliferation and invasion in osteosarcoma by targeting Sirt1. Oncol Res. 2017;25:1421–30.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Zhou W, Hao M, Du X, Chen K, Wang G, Yang J. Advances in targeted therapy for osteosarcoma. Discov Med. 2014;17:301–7.

    PubMed  Google Scholar 

  8. Chunder N, Basu D, Roy A, Roychoudhury S, Panda CK. Prediction of retinoblastoma and osteosarcoma: linkage analysis of families by using polymorphic markers around RB1 locus. J BUON. 2003;8:365–9.

    CAS  PubMed  Google Scholar 

  9. Chen Z, Guo J, Zhang K, Guo Y. TP53 mutations and survival in osteosarcoma patients: a meta-analysis of published data. Dis Markers. 2016;2016:4639575.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Yang J, Yang D, Cogdell D, et al. APEX1 gene amplification and its protein overexpression in osteosarcoma: correlation with recurrence, metastasis, and survival. Technol Cancer Res Treat. 2010;9:161–9.

    Article  CAS  PubMed  Google Scholar 

  11. Bao Y, Chen B, Wu Q, et al. Overexpression of miR-664 is associated with enhanced osteosarcoma cell migration and invasion ability via targeting SOX7. Clin Exp Med. 2017;17:51–8.

    Article  CAS  PubMed  Google Scholar 

  12. Li YJ, Dai YL, Zhang WB, Li SJ, Tu CQ. Clinicopathological and prognostic significance of chemokine receptor CXCR12 in patients with bone and soft tissue sarcoma: a meta-analysis. Clin Exp Med. 2015;17:1–11.

    Google Scholar 

  13. Pure E, Blomberg R. Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics. Oncogene. 2018;37:4343–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang HE, Hamson EJ, Koczorowska MM, et al. Identification of novel natural substrates of fibroblast activation protein-alpha by differential degradomics and proteomics. Mol Cell Proteomics. 2019;18:65–85.

    Article  CAS  PubMed  Google Scholar 

  15. Brokopp CE, Schoenauer R, Richards P, et al. Fibroblast activation protein is induced by inflammation and degrades type I collagen in thin-cap fibroatheromata. Eur Heart J. 2011;32:2713–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Panaro BL, Coppage AL, Beaudry JL, et al. Fibroblast activation protein is dispensable for control of glucose homeostasis and body weight in mice. Mol Metab. 2019;19:65–74.

    Article  CAS  PubMed  Google Scholar 

  17. Fan MH, Zhu Q, Li HH, et al. Fibroblast activation protein (FAP) accelerates collagen degradation and clearance from lungs in mice. J Biol Chem. 2016;291:8070–89.

    Article  CAS  PubMed  Google Scholar 

  18. Wong PF, Gall MG, Bachovchin WW, McCaughan GW, Keane FM, Gorrell MD. Neuropeptide Y is a physiological substrate of fibroblast activation protein: enzyme kinetics in blood plasma and expression of Y2R and Y5R in human liver cirrhosis and hepatocellular carcinoma. Peptides. 2016;75:80–95.

    Article  CAS  PubMed  Google Scholar 

  19. Kelly T, Huang Y, Simms AE, Mazur A. Fibroblast activation protein-alpha: a key modulator of the microenvironment in multiple pathologies. Int Rev Cell Mol Biol. 2012;297:83–116.

    Article  CAS  PubMed  Google Scholar 

  20. Kashima H, Noma K, Ohara T, et al. Cancer-associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma. Int J Cancer. 2019;144:828–40.

    Article  CAS  PubMed  Google Scholar 

  21. Wang RF, Zhang LH, Shan LH, et al. Effects of the fibroblast activation protein on the invasion and migration of gastric cancer. Exp Mol Pathol. 2013;95:350–6.

    Article  CAS  PubMed  Google Scholar 

  22. Cao F, Wang S, Wang H, Tang W. Fibroblast activation protein-alpha in tumor cells promotes colorectal cancer angiogenesis via the Akt and ERK signaling pathways. Mol Med Rep. 2018;17:2593–9.

    CAS  PubMed  Google Scholar 

  23. Tian DW, Wu ZL, Jiang LM, Gao J, Wu CL, Hu HL. Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer. Cancer Sci. 2019;110:458–67.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang XG, Zhang T, Li CY, Zhang MH, Chen FM. CD164 promotes tumor progression and predicts the poor prognosis of bladder cancer. Cancer Med. 2018;7:3763–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Koksal H, Muller E, Inderberg EM, Bruland O, Walchli S. Treating osteosarcoma with CAR T cells. Scand J Immunol. 2019;89:e12741.

    Article  PubMed  Google Scholar 

  26. Xu J, Xie L, Guo W. Neoadjuvant chemotherapy followed by delayed surgery: is it necessary for all patients with nonmetastatic high-grade pelvic osteosarcoma? Clin Orthop Relat Res. 2018;476:2177–86.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Jia J, Martin TA, Ye L, Jiang WG. FAP-alpha (fibroblast activation protein-alpha) is involved in the control of human breast cancer cell line growth and motility via the FAK pathway. BMC Cell Biol. 2014;15:16.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zhang YQ, Lu JX, Sun HX, et al. Expression of fibroblast activation protein in HBV related hepatocellular carcinoma. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2011;25:463–5.

    CAS  PubMed  Google Scholar 

  29. Christiansen VJ, Jackson KW, Lee KN, Downs TD, McKee PA. Targeting inhibition of fibroblast activation protein-alpha and prolyl oligopeptidase activities on cells common to metastatic tumor microenvironments. Neoplasia. 2013;15:348–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zeng C, Wen M, Liu X. Fibroblast activation protein in osteosarcoma cells promotes angiogenesis via AKT and ERK signaling pathways. Oncol Lett. 2018;15:6029.

    PubMed  PubMed Central  Google Scholar 

  31. Wang H, Wu Q, Liu Z, et al. Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. Cell Death Dis. 2014;5:e1155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jia J, Martin TA, Ye L, et al. Fibroblast activation protein-alpha promotes the growth and migration of lung cancer cells via the PI3K and sonic hedgehog pathways. Int J Mol Med. 2018;41:275–83.

    CAS  PubMed  Google Scholar 

  33. Zhang J, Valianou M, Cheng JD. Identification and characterization of the promoter of fibroblast activation protein. Front Biosci (Elite Ed). 2010;2:1154–63.

    PubMed  PubMed Central  Google Scholar 

  34. Haim Y, Bluher M, Slutsky N, et al. Elevated autophagy gene expression in adipose tissue of obese humans: a potential non-cell-cycle-dependent function of E2F1. Autophagy. 2015;11:2074–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zheng C, Ren Z, Wang H, et al. E2F1 Induces tumor cell survival via nuclear factor-kappaB-dependent induction of EGR1 transcription in prostate cancer cells. Cancer Res. 2009;69:2324–31.

    Article  CAS  PubMed  Google Scholar 

  36. Balaziova E, Busek P, Stremenova J, et al. Coupled expression of dipeptidyl peptidase-IV and fibroblast activation protein-alpha in transformed astrocytic cells. Mol Cell Biochem. 2011;354:283–9.

    Article  CAS  PubMed  Google Scholar 

  37. Huang Y, Simms AE, Mazur A, et al. Fibroblast activation protein-alpha promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions. Clin Exp Metastasis. 2011;28:567–79.

    Article  CAS  PubMed  Google Scholar 

  38. Ge Y, Zhan F, Barlogie B, Epstein J, Shaughnessy J Jr, Yaccoby S. Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival. Br J Haematol. 2006;133:83–92.

    Article  CAS  PubMed  Google Scholar 

  39. Juillerat-Jeanneret L, Tafelmeyer P, Golshayan D. Fibroblast activation protein-alpha in fibrogenic disorders and cancer: more than a prolyl-specific peptidase? Expert Opin Ther Targets. 2017;21:977–91.

    Article  CAS  PubMed  Google Scholar 

  40. Liu R, Li H, Liu L, Yu J, Ren X. Fibroblast activation protein: a potential therapeutic target in cancer. Cancer Biol Ther. 2012;13:123–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Not applicable.

Author information

Author notes

  1. Li Yang, Liang Zhang and Zi-Wei Xia have contributed equally to this study.

Authors and Affiliations

  1. Department of Orthopedics, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China

    Liang Zhang, Li Yang, Zi-Wei Xia, Shi-Chang Yang, Wen-Hui Li, Zi-Qi Yu, Peng-Fei Gong, Ya-Lin Yang, Wei-Zong Sun & Kai Wang

  2. Department of Gastrointestinal Surgery, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China

    Bin Liu

  3. Department of Pathology, Tianjin Medical University, Tianjin, 300070, China

    Jing Mo

  4. Department of Joint Orthopedics, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong Province, China

    Gui-Shi Li

  5. Department of Orthopedics, The 981st Hospital of the Chinese People’s Liberation Army, Chengde, 067000, Hebei Province, China

    Tian-Yi Wang

Authors
  1. Liang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zi-Wei Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shi-Chang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wen-Hui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zi-Qi Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peng-Fei Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ya-Lin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wei-Zong Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jing Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Gui-Shi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tian-Yi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kai Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Tian-Yi Wang or Kai Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All experimental procedures were performed according to the Declaration of Helsinki. The study protocol was approved by IACUC of The Second Hospital of Tianjin Medical University.

Informed consent

Informed consent was obtained from all participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1007/s10238-023-01211-0

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1. The detailed information of shRNA. (DOC 32 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, L., Yang, L., Xia, ZW. et al. RETRACTED ARTICLE: The role of fibroblast activation protein in progression and development of osteosarcoma cells. Clin Exp Med 20, 121–130 (2020). https://doi.org/10.1007/s10238-019-00591-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-019-00591-6

Keywords

Search

Navigation